rs10231416

Positions:

• chr7-51145910-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015198.5(COBL):​c.784-9579A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,148 control chromosomes in the GnomAD database, including 2,690 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2690 hom., cov: 32)
• Consequence: COBL NM_015198.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

Genes affected

COBL (HGNC:22199): (cordon-bleu WH2 repeat protein) This gene encodes a protein that contains WH2 domains (WASP, Wiskott-Aldrich syndrome protein, homology domain-2) that interact with actin. The encoded actin regulator protein is required for growth and assembly of brush border microvilli that play a role in maintaining intestinal homeostasis. A similar protein in mouse functions in midbrain neural tube closure. A pseudogene of this gene is located on chromosome X. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COBL	NM_015198.5	c.784-9579A>C		intron_variant		ENST00000265136.12	NP_056013.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COBL	ENST00000265136.12	c.784-9579A>C		intron_variant		1	NM_015198.5	ENSP00000265136	P2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24013 AN: 152030 Hom.: 2676 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 24078 AN: 152148 Hom.: 2690 Cov.: 32 AF XY: 0.161 AC XY: 11956 AN XY: 74390

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0767

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0969 Hom.: 1983

Bravo AF: 0.171

Asia WGS AF: 0.191 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10231416; hg19: chr7-51213607; COSMIC: COSV54349823;